Pharmacology 203 Windward Community College

Sedatives, Hypnotics Anxiolytics and Mood Stabilizers

We are starting psychotherapeutics

In this lecture we will look at drugs with lots of

overlapping indications.

GABA-A agonists

Benzodiazepines

o Alprazolam

o Diazepam

o Lorazepam

o Midazolam

Non-benzodiazepine

hypnotics

o Zolpidem

o Eszopiclone

Barbiturates

o Phenobarbital

Certain antiepileptic drugs

o Pregabalin

Certain general anesthetics

o Propofol

GABA-A agonists are not the only ones with sedating effects.

Anticholinergics, including 1st generation antihistamines, blockers,

antidepressants and antipsychotics, among others, may too.

GABA-A agonists GABA is a neurotransmitter that acts upon the GABA-A receptor

to negatively modulate the activity of other neurons. That

means it inhibits their activity, slows them down, dampens their

actions. It should be easy to see then, how a drug that mimics

this neurotransmitter should have calming, sedating, hypnotic

effects.

Alcohol (ethanol) is a GABA-A agonist. If you can remember the

effects of alcohol and that they are dose-related, it will help you

with all the other GABA-A agonists. The effects of alcohol

include:

At a low dose: euphoria, decreased anxiety, increased

sociability, impaired judgment and shortened attention span.

At a moderate dose: sedation, impaired memory and

understanding, delayed reactions, impaired muscle

coordination (ataxia, blurred vision), dizziness, impaired speech.

At high doses: Lapses of consciousness, respiratory depression,

anterograde amnesia, vomiting, incontinence, depressed

reflexes, decreased heart rate, severe CNS depression, coma…

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Pharmacology 203 Windward Community College

Sedative Hypnotic Drugs

Benzodiazepines, BZD (all C-IV)

Alprazolam (Xanax) is used orally as an anxiolytic. It has active

metabolites.

Lorazepam (Ativan) does not have active metabolites. It is now

a drug of choice for status epilepticus. Lorazepam is currently

on the FDA drug shortage list (as of Nov 2012).

Diazepam (Valium) has active metabolites and unpredictable

kinetics. Genetic differences in metabolism make this drug

interesting. It is still used for many purposes on and off label,

including acute alcohol withdrawal.

Midazolam (Versed, Hypnovel) has active metabolites, but has

a very short duration of action, for hypnosis, only about 2 hours.

Midazolam is used in surgery as part of the anesthetic cocktail,

to promote anxiolysis, sedation and memory loss. It is very

dangerous due to respiratory depression, though.

All BZD and non-BZD hypnotics are on the Beer’s List.

Become Familiar with the Beer’s List

The Beer’s List is an important resource. It

provides information on drugs potentially

hazardous to the elderly.

http://www.americangeriatrics.org/files/docum

ents/beers/2012BeersCriteria_JAGS.pdf

http://www.americangeriatrics.org/health_care

_professionals/clinical_practice/clinical_guideli

nes_recommendations/2012

http://www.americangeriatrics.org/files/docum

ents/beers/FHATipMEDS.pdf

Non-BZD hypnotics These drugs act just like BZD and are all C-IV.

Zolpidem (Ambien, Intermezzo, Zolpimist) and

Eszopiclone (Lunesta) are used for short-term

treatment of insomnia. The doses should be halved

in women, the elderly and for eszopiclone, liver

patients.

Both are associated with somnambulism, or

“sleepwalking.” Patients exhibiting this behavior

may appear to be completely awake and talk or

carry out other seemingly normal activities (like

cooking, or driving).

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Pharmacology 203 Windward Community College

Other Sedatives and Hypnotics

The barbiturates are also GABA-A agonists. All of

the barbiturates induce P450s, some, like

phenobarbital, very strongly so. The barbiturates

fall into two basic classes, those that are highly lipid

soluble, like thiopental (also known as pentothal),

and the more polar barbiturates like phenobarbital

(luminal). The lipid soluble drugs tend to have a

more rapid onset and are C-III. The polar drugs

often last longer and are C-IV.

In subhypnotic doses, phenobarbital is antiepileptic.

Unfortunately, the long duration of action typically

causes considerable drowsiness, or drug-hangover,

until the patient becomes tolerant to the drug.

Thiopental, a drug used in states with “death-by-

lethal-injection” sentences in their judicial system, is

becoming very difficult to get.

Sedating antihistamines like diphenhydramine

(Benadryl, Sominex) are often used OTC as a short-

term hypnotic.

The type of sleep induced by all the sedative

hypnotic drugs differs from physiologic sleep.

Patients should be advised to not suddenly

discontinue their medications if used regularly as

they may experience markedly increased

dreaming, nightmares and often, insomnia.

Therefore, patients taking hypnotics should be

gradually weaned off their medication over several

days to a week.

Buspirone (BuSpar) is indicated for

anxiety disorders. It isn’t

understood how Buspirone works. It

has a high affinity for 5-HT1a

receptors and moderate affinity for

dopamine (D2) receptors.

Propranolol (Inderal) is anxiolytic

because it interrupts the

sympathetic nervous system

response to stress. Because of this,

propranolol has great promise in

actually curing (in some people)

post-traumatic stress disorder

(PTSD).

Other anxiolytics include AEDs like

Topiramate, Pregabalin and

Gabapentin and antidepressants

including the SSRIs.

Non Sedating Anxiolytics

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Pharmacology 203 Windward Community College

Mood stabilizers are used in the treatment of bipolar

disorder. There are a number of unrelated drugs used,

which share a number of warnings, including increased risk

of:

Suicide (especially the antidepressants) NOT lithium,

which decreases the risk of suicide;

Psychosis (a risk with bipolar anyway)

Arrhythmias or seizures

Discontinuation syndrome

Significant weight gain

Lithium (Lithane, Happy Happy, Eskalith, Lithobid) was used

in the 1800’s to treat gout because it increases the water

solubility of uric acid. In the 1940’s an Australian psychiatrist

accidentally discovered that lithium had a calming effect.

Lithium has a very narrow therapeutic margin. Therapeutic

levels are usually between 0.6-1.2 mEq/L, while toxicity

begins at 1.5 mEq/L. Many patients were poisoned before

a reliable blood test was developed to monitor lithium

levels. Patients taking lithium must be monitored every 3-6

months once levels are stable. For information on the test

and additional monitoring, click HERE.

Carbamazepine (Equetro, Tegretol) is an antiepileptic drug

(AED) indicated to treat epilepsy, mania associated with

bipolar disorder and trigeminal neuralgia. It is used for

many other purposes. It has a number of boxed warnings,

including a risk of Steven Johnson’s syndrome (SJS).

http://www.drugs.com/monograph/carbamazepine.html

Bipolar Disorder

Bipolar disorder affects

between 1-3% of the

population with many

individuals being

undiagnosed and/or

untreated.

The average age of

onset for bipolar disorder

is 17 years old and is most

often triggered by sleep

deprivation.

10% of bipolar patients

will commit suicide.

Because the manic

phase of bipolar disorder

is so euphoric, and most

of the medications used

to treat the condition

dampen the high energy

levels associated with

the manic phase,

medication compliance

is poor in this patient

population.

Mood Stabilizers

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Pharmacology 203 Windward Community College

Divalproex (Depakote) is a 50:50 mixture of

valproate and valproic acid. Valproate

(Depacon) is a Prodrug converted to

valproic acid (Depakene) in the stomach.

They are AEDs with many other uses

including mania associated with bipolar

disorder, migraine, and as an adjunct to

schizophrenia treatment in patients with

agitated, aggressive or violent behavior.

Lamotrigine (Lamictal) is another AED with

many uses. It is indicated for epilepsy and

for maintenance treatment of bipolar 1

disorder.

Other drugs used in

bipolar therapeutics Doxepin (Sinequan) an antidepressant, is

used to treat bipolar depression as is the

mixture of Fluoxetine, another

antidepressant, with Olanzapine, an

antipsychotic, which are formulated into the

popular fixed-dose combination Symbyax.

A number of antipsychotics are used, alone

or in combination therapy, including

Olanzapine (Zyprexa), Risperidone

(Risperdal), Quetiapine (Seroquel),

Ziprasidone (Geodon) and Aripiprazole

(Abilify).

(continued)

Pharmacology 203 Windward Community College

Lithium side effects

Substantial weight gain – 30% become obese

Tremors – up to 60% of patients develop tremors

Goiter – up to 90% of patients develop thyroid problems

Alopecia – 20% will lose their hair

Teratogenic in 1st trimester

Loss of visual accommodation

Memory loss

Skin effects – especially acne and rashes

The risk of toxicity and side effects is increased by:

NSAIDs

Thiazide diuretics

Dehydration

Sleep is critical to a healthy mind.

Homework and Exercises 1. Read the “START HERE” announcement in Laulima for updates and instructions.

2. Read about Sedative, Hypnotic, Anxiolytic, and Mood Stabilizing drugs in Chapter 22 & 23,

Pharmacology of Anxiety and Sleep Disorders & Pharmacology of Mood Disorders. Adams &

Urban, PHARMACOLOGY Connections to Nursing Practice.

3. Review the Powerpoints and listen to the audio from the face-to-face lecture. You may opt to

watch the appropriate videos for this lecture. Review any handouts available for this lecture in

the Course Index.

4. Complete the SLO practice set for Sedatives, Hypnotics, Anxiolytics and Mood Stabilizers in Tasks,

Tests and Surveys.

5. Use “Chat,” “Discussions and Private Messages” or the lecture “Forum” to ask questions and find

answers or to seek assistance.

6. Complete the online quiz in Laulima, Tasks, Tests and Surveys.

If you have any questions, email me at abeale@hawaii.edu